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Biomedical subjects

S Ikawa

Publications and source records attributed to S Ikawa.

At least 145 records · Page 8Linked to original sources

Activation of the cellular src gene by transducing retrovirus.

Newly isolated strains of avian sarcoma virus, S1 and S2, were shown to have the transduced cellular src gene as their viral transforming gene (Yamagishi et al., Virology 137:266-275, 1984). In this work, the S1 and S2 genomes were molecularly cloned, and the junction sequences between the viral genomes and the c-src genes and the complete nucleotide sequences of the v-src genes transduced in these viruses were determined. Data on the junction sequences suggested that 5' recombination had occurred between the 5'-noncoding region of c-src and the 5' region of the gag sequence encoding p19 in both viruses and that 3' recombination had occurred in the last coding exon of c-src with either the middle portion of the env sequence encoding gp85 for S1 or the 3' portion of pol coding for reverse transcriptase for S2. Comparison of the amino acid sequences of the S1 and S2 src products deduced from the nucleotide sequences (pp62S1-src and pp62S2-src with that of c-src protein (pp60c-src) indicated that in pp62S1-src the 8 carboxy-terminal amino acid residues of the total of 533 in pp60c-src are replaced by 43 residues translated from the env sequence at the wrong frame. In pp62S2-src, on the other hand, the 14 carboxy-terminal amino acids of pp60c-src are replaced by the 38 carboxy-terminal residues of reverse transcriptase. The mechanism of c-src transduction and the structural changes necessary for pp60c-src activation are discussed.

Animals↗

Age- and sex-related profiles of serum primary and total bile acids in infants, children and adults.

The relation of age and sex to serum primary (PBA) and total bile acid (TBA) concentrations was evaluated by an enzymatic fluorometric microassay in healthy infants, children and adults. TBA concentrations were the highest in the 6-day-old group and 1-month-old group and seemed to switch to almost normal adult levels by the age of 4-6 years, which persisted throughout life, while PBA concentrations were predominant over a period of 3 days to 3 months after birth. No sex-related differences were observed from neonates to very old persons for any of serum bile acids. These results show that the bile acid metabolism in the liver and the enterohepatic circulation of bile acids are usually matured in infancy and that aging and sex may insignificantly affect serum bile acid metabolic profiles.

Adolescent↗

Modification of carboxyl-terminal region is the cause of activation of the src gene in avian sarcoma virus S2.

Viral oncogene product of avian sarcoma virus S2 was reported to have two alterations from proto-src product; a substitution of its extreme carboxyl terminus with a peptide of helper viral protein and a point mutation which altered the 501st amino acid from arginine to lysine. However, the following data suggest that lysine501 is more common in proto-src product than arginine501. Proto-src from two independent embryos which we analyzed encoded lysine for the 501st amino acid. Rous sarcoma virus and S1, another isolate which had transduced proto-src, also coded for lysine at the same position. Thus, in the case of S2, the oncogenic activation of the src gene appeared to be achieved with only an alteration at its carboxyl terminus and enhanced expression by long terminal repeats.

Amino Acid Sequence↗

Sterol and bile acid metabolism after short-term prednisolone treatment in patients with chronic active hepatitis.

Serum levels of squalene, cholesterol and bile acid were measured before and after short-term prednisolone administration in patients with chronic active hepatitis. Comparison with normal controls indicated that serum bile acid levels were increased significantly (p less than 0.01) in patients with chronic active hepatitis, but serum levels of squalene and cholesterol did not differ significantly between the two groups. After short-term prednisolone treatment, serum levels of squalene and cholesterol were increased significantly (p less than 0.01) as compared with the pretreatment level. On the other hand, while serum fasting bile acid levels were found to be increased significantly (p less than 0.01), serum clearance after oral administration of ursodeoxycholic acid improved significantly (p less than 0.05) after treatment. These results indicated that short-term prednisolone treatment increases sterol metabolism in the liver in patients with chronic active hepatitis, resulting from an increase in hepatic clearance of bile acids.

Adolescent↗

Measurement of the ratio of primary to total bile acids in serum by enzymatic fluorometric microassay and its clinical significance in patients with liver disease.

An enzymatic fluorometric microassay using 3 alpha- or 7 alpha-hydroxysteroid dehydrogenase was devised to determine serum total or primary bile acids. The present microassay using 50 microliter of a serum sample was run as a two-step method; the first step is the reaction of substrates with NAD+ and the hydroxysteroid dehydrogenase to produce as much NADH as possible in the incubation system and the second step is that of NADH with resazurin coupled with 1-methoxy phenazinemethosulfate to produce fluorescent resorfin. The assay is specific for 3 alpha- or 7 alpha-hydroxy bile acids, sensitive (a detection limit of 1.5 microM with a linear range of 1.5-80 microM), reproducible (CV = less than 5%) and inexpensive. As measured by this microassay, the ratio of serum primary to total bile acids (P/T ratio) in 10 normal subjects was 62.1 +/- 0.7% and was significantly elevated in the early phase of acute hepatitis (p less than 0.01), followed by return to the normal level after 4 weeks.

3-Hydroxysteroid Dehydrogenases↗

Characterization of two strains of avian sarcoma virus isolated from avian lymphatic leukosis virus-induced sarcomas.

Two replication-defective avian sarcoma viruses, S1 and S2, which were independently isolated from tumors of chickens inoculated with avian lymphatic leukosis virus (LLV) were characterized. The genomes of S1 and S2 contain src-related sequences and are, respectively, about 3.9 and 4.5 kilobases long. pp60src-related proteins with molecular weights of 62,000 (p62) were detected in cells infected with these viruses, and protein kinase activity was found to be associated with these proteins. No other viral proteins, such as gag, pol, and env gene products, were detected. These results suggested that the c-src sequence in normal chicken cells was incorporated into LLV genomes by recombination at the expense of most of the viral genes to generate highly defective new sarcoma viruses.

Alpharetrovirus↗

Nucleotide sequence of the tobacco mosaic virus (tomato strain) genome and comparison with the common strain genome.

The sequence of about 4,500 nucleotides of the internal part of tobacco mosaic virus (TMV)-tomato strain (L) RNA has been newly determined using cloned cDNAs. Together with the previously determined partial sequences at both ends, the entire sequence of the 6,384 nucleotide genome has been completed. The 130K (1,115 amino acids), 180K (1,615 amino acids), 30K (263 amino acids) and coat protein (158 amino acids) cistrons are located at residues 72-3442, 72-4922, 4906-5700, and 5703-6182 on the genome, respectively. Sequence polymorphism was not observed except for heterogeneity in the length of the A cluster near the 3' end. The homology of the nucleotide sequences of TMV-L and TMV-vulgare, a common strain, is about 80% on average. Remarkable differences between them were found in a part of the N-terminal portion of the 130K/180K protein and the C-terminal portion of the 30K protein. A new method for cDNA cloning was developed by which the cDNA of the 5'-terminus of viral RNA can be cloned efficiently.

Base Sequence↗

Role of portal and splenic vein shunts and impaired hepatic extraction in the elevated serum bile acids in liver cirrhosis.

To study the mechanism for the elevation of serum bile acids in liver cirrhosis, bile acid concentrations were measured in the portal, superior mesenteric, and splenic veins, using percutaneous transhepatic catheterization, and compared with those of peripheral veins in 41 patients with mild to moderately advanced cirrhosis. The demonstrated gradient of bile acid concentration was superior mesenteric vein greater than portal vein greater than peripheral vein nearly equal to splenic vein, suggesting that the superior mesenteric vein is the main route of transport for the intestinally absorbed bile acids. Bile acid concentrations in peripheral vein were correlated with the measured portal and splenic vein shunt indexes. The ursodeoxycholic acid oral tolerance test carried out in 10 patients during portal vein catheterization demonstrated that hepatic extraction of this bile acid was correlated with indocyanine green clearance and that it was inversely correlated with portal vein shunt index. These findings are consistent with the view that distorted hepatic blood flow has a significant role in elevating serum bile acid, at least in patients with moderately advanced liver cirrhosis.

Adolescent↗

Distribution of Hp, Tf, Gc and Pi polymorphisms in a Nepalese population.

Hp typing and Tf, Gc and Pi subtypings were performed on 144 serum samples from a Nepalese population in the Katmandu Valley, Nepal. The obtained allele frequencies are as follows: Hp1 = 0.1771, Hp2 = 0.8229; TfC1 = 0.7222, TfC2 = 0.2500, TfC3 = 0.0174, TfCnepal (TfC9) = 0.0104; Gc1F = 0.2448, Gc1S = 0.4825, Gc2 = 0.2727; PiM1 = 0.6076, PiM2 = 0.2118, PiM3 = 0.1806. The relationship between this sample population and the Indian population is discussed.

Blood Proteins↗

Fecal bile acids and neutral sterols in Japanese with large bowel carcinoma.

We compared the level of fecal bile acids and neutral sterols in 15 Japanese with large bowel carcinoma and 10 healthy controls. There was no significant difference in the amount of total fecal bile acids and neutral sterols between the patients and the controls. However, the amount of primary bile acids, especially chenodeoxycholic acid, tended to be higher in the patients. Conversely, lithocholic, beta-lithocholic and 3 alpha-hydroxy-12-ketocholanoic acid levels were higher in the controls. Trace amounts of 3 alpha-hydroxy-6-ketocholanoic acid were detected in some of the patients; none was found in the controls. Although a hasty conclusion should be avoided in the present study, it is of considerable interest that there was a difference in fecal bile acid composition between large bowel carcinoma patients and healthy controls.

Aged↗